As an SP1-driven Tataless promoter domain was localized within the 173 bp 5' flanking region of luteinizing hormone receptor gene. Within this region cis-elements and transbinding factors responsible for stimulatory/inhibitory control of the gene and tissue-specific expression were identified. Transcription is dependent on the presence of two SP1 elements (Sp1/2 and SP/4) that contribute equally to transcript initiation. Promoter activity is regulated by at least three additional DNA domains [R domain (-1266 to -1307 bp), C-box (-42 to -73 bp, and M1 (- 24 to -42 bp)] that bind multiple transfactors in a tissue-specific manner. Basal promoter activity is dependent on a functional M1 domain in LH receptor-expressing mouse Leydig tumor cells (mLTC) but not in non- expressing CHO cells. The C-box binding factors either inhibit promoter activity or block inhibition through overlapping but non-identical DNA binding domains (AP-2 and NF-1 elements). Removal of the AP-2 element in the C-box results in mLTC-specific transcriptional activation that may involve an mLTC M1/C-box interaction. In addition, competition for C-box factors by an upstream regulatory element that is only inhibitory in CHO cells indicates that both the C-box inhibitory AP-2 protein and the C-box neutral NF-1 proteins compete for this upstream domain in a tissue- specific manner. Competition between the inhibitory and neutral DNA binding factors within both upstream and promoter domain could provide a mechanism for the control of LH receptor gene expression in gonadal cells. Within the 6.2 kb of the 3' non-coding region of the gene, two functional pA domains (H1 and H2) produce two sets of major mRNA transcripts of 2.6/2.3 kb encoding the holoreceptor and alternatively spliced B form, respectively, and the corresponding high MW (5.8 and 5.5) mRNAs for both forms. The functional efficiency of each pA domains is related to the intrinsic nature of the pA signals and is enhanced 5-7 fold in the presence of downstream genomic sequence of up to 12.6 kb 3' to H1, or l.3 kb 3' to H2; it is also influenced by tissue-specific factors. An insertion of the functional pA domain (H1) and the known trasposon R domain (a repetitive DNA line R domain) in the LHR gene is postulated to have occurred following divergence from the TSHR and FSHR genes in evolution.